Slow Penetration of Thyrotropin‐Releasing Hormone Across the Blood‐Brain Barrier of an In Situ Perfused Guinea Pig Brain

Abstract

Transport of ³H-labelled thyrotropin-releasing hormone (TRH) across the blood-brain barrier was studied in the ipsilateral perfused in situ guinea pig forebrain. The unidirectional transfer constant (K_in) calculated from the multiple time brain uptake analysis ranged from 1.14 × 10-⁻³ to 1.22 × 10-⁻³ ml min⁻¹ g⁻¹, in the parietal cortex, caudate nucleus, and hippocampus. Regional K_in values for [³H]TRH were significantly reduced by 43–48% in the presence of an aminopeptidase and amidase inhibitor, 2 mM bacitracin, suggesting an enzymatic degradation of tripeptide during interaction with the blood-brain barrier. In the presence of unlabelled 1 mM TRH and 2 mM bacitracin together, a reduction of [³H]TRH regional K_in values similar to that obtained with 2 mM bacitracin alone was obtained. l-Prolinamide, the N-terminal residue of tripeptide, at a 10 mM level had no effect on the kinetics of entry of [³H]TRH into the brain. The data indicate an absence of a specific saturable transport mechanism for TRH presented to the luminal side of the blood-brain barrier. It is concluded that intact TRH molecule may slowly penetrate the blood-brain barrier, the rate of transfer being some three times higher than that of d-mannitol.